Metabolic regulation of activins in healthy individuals and in obese patients undergoing bariatric surgery

Abstract

ObjectiveFollistatin binds and inactivates activins, which are potent inhibitors of muscle growth and metabolism and are currently being developed for the treatment of obesity and type 2 diabetes (T2D). We have recently reported that follistatin is regulated by glucose (and not lipids) and can prospectively predict the metabolic improvements observed after bariatric surgery. We utilized novel assays herein to investigate whether activins are regulated by glucose or lipids, whether their circulating levels change after bariatric surgery and whether these changes are predictors of metabolic outcomes up to 12 months later.Design and MethodsActivin A, B, AB and their ratios to follistatin were measured in (a) healthy humans (n = 32) undergoing oral or intravenous lipid or glucose intake over 6 h, (b) morbidly obese individuals with or without type 2 diabetes undergoing three different types of bariatric surgery (gastric banding, Roux‐en‐Y bypass or sleeve gastrectomy) in two clinical studies (n = 14 for the first and n = 27 for the second study).ResultsGlucose intake downregulates circulating activin A, B and AB, indicating the presence of a feedback loop. Activin A decreases (~30%), activin AB increases (~25%) and activin B does not change after bariatric surgery. The changes in activin AB and its ratio to follistatin 3 months after bariatric surgery can predict the BMI reduction and the improvement in insulin and HOMA‐IR observed 6 months postoperatively.ConclusionActivins are implicated in glucose regulation in humans as part of a feedback loop with glucose or insulin and predict metabolic outcomes prospectively after bariatric surgery.

Follistatin as a Potential Biomarker for Identifying Metabolically Healthy and Unhealthy Obesity: A Cross-Sectional Study

“…In a study by Perakakis et al, the follistatin levels decreased significantly after oral or intravenous glucose administration [25]. The circulating follistatin levels were lower after bariatric surgery, particularly after Rouxen-Y gastric bypass, and the reduction in the circulating follistatin levels was associated with improved glucose homeostasis and body fat mass after surgery [24].…”

“…Our results are consistent with those of previous studies, suggesting that insulin may have a regulatory effect on follistatin levels. Follistatin is regulated by glucose and can prospectively predict metabolic improvements observed after bariatric surgery [24]. In a study by Sylow et al, the fasting plasma follistatin levels were strongly correlated with fasting hyperinsulinemia and insulin resistance in patients with type 2 diabetes [22].…”

Relationship to Bariatric Surgery and their Gastrointestinal Hormones: how we Weight Loss?

“…More benefits were seen in Gastric Bypass when compared to Sleeve Gastrectomy for controlling obesity, metabolic syndrome, decreased insulin metabolism, maintenance of long-term weight loss, and improvement of comorbidities [18][19][20][21][22][23][24][25][26][27][28][29][30].…”

Serum levels of Activin A: Marker of insulin resistance and cardiovascular risk in prediabetics

“…[ 14 15 ] Perakakis et al . [ 16 ] reported a significant positive correlation of activin A with BMI and HOMA-IR ( r = 0.339, P < 0.001; r = 0.211, P < 0.05, respectively) and concluded activin A to be implicated in glucose regulation as a part of a feedback loop including glucose or insulin.…”